The proposed research deals with four areas of investigation: (1) reconstruction of the prothrombinase complex, (2) regulation of the prothrombin complex and the blood coagulation process by the fragments, intermediates and products of prothrombin activation. (3) the regulation of prothrombin biosynthesis by prothrombin activation products. (4) the evaluation of the possible uses of the prothrombin activation fragments and specific antibodies directed toward them as diagnostic tools for the diffuse intravascular clotting syndrome. Reconstruction studies involve the isolation of factor V and platelet membrane for studies of the biology and structure of the purified prothrombinase complex. These studies also involve searches for additional intermediates of the prothrombin activation products. These studies will be complemented with studies conducted in complete biological systems with (H3) sialyl prothrombin. Regulation studies will involve initially the effect of intermediate 3 and intermediate 4 on prothrombinase and thrombin and include studies of the binding of intermediate 4 to thrombin and the specificity of the intermediate 4 thrombin complex. Biosynthetic studies involve the infusion of canine prothrombin intermediates into dogs and the measurement of their turnover and their effect of prothrombin plasma levels.